Microtubules and Mechanical Stresses

Essential Info: What is the Role of Microtubules in Mechanotransduction?

6.5 Microtubules and Mechanical Stress

Microtubules exist in all cells, however their influence in the mechanotransduction of mechanical stimuli has been described at length in cardiac striated muscle [1] and as such these findings are summarised here:

Mechanical Stimuli Affect Microtubule Formation and Proliferation

Passive stretching of cardiac muscle is one example where mechanical stimuli affects microtubule formation. In this case, tubulin mRNA and protein levels were shown to be upregulated in response to the passive stretching of neonatal cardiac myocytes [2]. These results were supported by findings of increased proliferation of microtubules following centrifugal force stretch of ventricular myocytes isolated from neonatal rats [3].

Intracellular Viscosity and Myocardiac Pressure Overload

Microtubule proliferation has been shown to increase the intracellular viscosity of myoctyes and impede sarcomere shortening, which is required to maintain contractility of the cardiac muscle [4]. Changes to these viscoelasticitic properties have been demonstrated in a number of in vitro experiments where physical stresses or the use of agents that selectively disrupt or promote microtubule formation, are applied to cells. In one such case, hypertensive ventricular myocytes were found to be stiffer and more viscous than normotensive ventricular myocytes, a property that was was removed following treatment with colchicine (an inhibitor of microtubule formation) [5].

It has been well established that myocardial pressure overloading, which results from ventricular hypertrophy, is associated with the loss of cardiac contractility in patients with heart failure [4]. Cooper et al attributed this to an increase in the density of microtubules within cardiac myocytes, where a viscous load is placed on the myofilaments and subsequently impedes sarcomere shortening. In support of their hypothesis, it was shown that treatment with microtubule depolymerizing agents such as colchicine increased contractility [4].

Impact on Electrical Activity of the Heart

It has also been reported that mechanotransduction of mechanical stimuli through the microtubule network affects the electrical activity of the heart [1]. This remains controversial however, with different studies reporting opposing findings depending on the model used. For example whilst colchicine treatment (and subsequent microtubule depolymerization) was found to promote arrhythmias in a swine model [6], it had no effect in rabbits [7].
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microtubulesandmechanicalstress.csv
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Sruthi Jagannathan,
Nov 7, 2012, 12:29 AM
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